ADRENERGIC

ADRENERGIC
RECEPTORS AND DRUGS
RECEPTORS AND DRUGS

PROF.
PROF.A.
A.K.
K.SAKSENA
SAKSENA
 ADRENERGIC RECEPTORS
ADRENERGIC RECEPTORS

α1 α2
-Postsynaptic Presyn. (periphery)
- Sm. M of peripheral B.V. - ↓ NT release
→vasoconstriction - ↓ Sym. Outflow
- Radial Mus. Of Iris - ↓ release of Insulin
→ mydriasis
* Phenylehrine * Clonidine
 ADRENERGIC
ADRENERGICRECEPTORS
RECEPTORS

β1 β2
Heart, JG cells - Bronchi, B.V. of deeper tissue,
Uterus, G.I.T.
↑ Cardiac activity - Relaxation of Sm. Muscles
↑ Renin - Liver & Sk. Musc.→ Glycogenolysis
* Isoprenaline - Pre-syn. on peripheral neurons
→ ↑ NT release
- Brain →↑ Sym. outflow
* Salbutamol
 ADRENERGIC RECEPTORS
ADRENERGIC RECEPTORS

β3
-Lipolysis

All are GPCRs.

 PHARMACOLOGICAL
PHARMACOLOGICALACTIONS
ACTIONS

Adrenaline is the prototype (α1, α2, β1, β2).

CNS:- in clinically used dose→ no effects
CVS:-
a) Heart:- (β1)
↑HR + ↑force of contraction →↑CO +↑ O2 consumption
Conduction velocity ↑ in conducting tissue
b) B.V.:- (α1 in periphery) → vasoconstriction
(β2 in deep) → vasodilation (Dale’s reversal)
c) BP:- ↑ during both systolic & diastolic phase
 PHARMACOLOGICAL
PHARMACOLOGICALACTIONS
ACTIONS(contd.)
(contd.)

Resp. Sys:- (β2) Bronchodilation

(α1) Decongestion of mucosa /submuc.

G.I.T:- (α1+β2) << important clinically- Relaxn

Eye:- (α1 on radial muscles) → Mydriasis.

Skeletal Musc:- (β2 on LMN terminals)

↑Release of ACh→ Twitching & Tremors.
 PHARMACOLOGICAL
PHARMACOLOGICALACTIONS
ACTIONS(contd.)
(contd.)

Metabolic:-
(β2) Glycogenolysis
(α2) ↓Release of Insulin→ Hyperglycemia
Uterus :- (β2) Relaxation
Spleen:- (α1) Contraction (not significant in
humans)
 ADRENERGIC DRUGS
ADRENERGIC DRUGS

Noradrenaline:- (NA) α1 ˃ α2 ˃ β1 = β3
Dopamine:- D and α & β1 (high dose)
D R in renal vessels → Dilation(low dose)
Dobutamine :- α and β1 (substitute)
Methoxamine :- α1 (BP)
Phenylephrine:- α1 Eye drops – Mydriasis
Isoprenaline :- β1 selective
 ADRENERGIC
ADRENERGICDRUGS
DRUGS(contd.)
(contd.)
Ephedrine:-
Acts by releasing NA (±Ad) stores
(facilitated diffusion)
Tachyphylaxis

Pseudoephedrine:-
Acts both by direct action (α1) and by releasing NT.

Phenylpropanolamine:- similar effects

 ADRENERGIC DRUGS (contd.)

Amphetamine- (Meth/Dextro/
Methylphenidate)
All act by direct and by releasing NTs
Prominent CNS effects:- ↑alertness, ↓sleep,
↑ concentration, generalized stimulation,
Suppression of appetite
Respiratory stimulation in Hypno-sedative poisoning
Banned drugs- athletes.
 ADRENERGIC DRUGS (contd.)
ADRENERGIC DRUGS (contd.)

Fenfluramine:-↓ appetite, sedation,

loss of libido(5-HT mech.)
Sibutramine:- Both NA/5-HT, (S/E mood swings)
Naphzoline As nasal decongestant (α1)
Oxymetazoline Mucosal necrosis & systemic S/E
Xylometazoline
Salbutamol, Terbutaline Selective β2, TBT
Salmeterol, Bambuterol Palpitation (β1),
Tremors (β2)
 ADRENERGIC DRUGS (contd.)
ADRENERGIC DRUGS (contd.)

Isoxsuprine:- β2- uterus→ Relaxation

β2- Deeper BV of Sk. M.→ dilation
Ritodrine:- β2 - Uterine relaxant
Clonidine:- α2 (presynaptic)
α-Methyl Dopa:- α2 (presynaptic)
Fenoldopam:- D1 (coronary, renal, mesentery)
 THERAPEUTIC USES
THERAPEUTIC USES
A) Vascular Uses
i) Hypotensive states:- Anaphylaxis- Ad.
Septic/ cardiogenic shock- DA, Dobutamine
ii) With LA:- Small dose; vasoconstriction
iii) In local bleeding:- Epistaxis- NOX
Gastric bleeding (ulcer)– NA in cold saline
iv) Nasal Decongestant- NOX, Pseudoephedrine
v) Peripheral vascular disease- Isoxsuprine
vi) Hypertension- Clonidine, α-Methyl Dopa.
 THERAPEUTIC USES (contd.)
THERAPEUTIC USES (contd.)

B) Cardiac Uses
i) AV Block- Adrenaline
ii) Cardiac Arrest- Adrenaline

C) Central Uses
i) Hypno-Sedative Poisoning- Amphetamines
ii) Narcolepsy- Amphetamines
iii) Hyperkinetic Children- Amphetamines
iv) Obesity- Fenfluramine, Sibutramine
v) De-addiction- Clonidine (alcohol / opioids)
 THERAPEUTIC USES (contd.)
THERAPEUTIC USES (contd.)
D) Respiratory- β2 agonists- Asthma
E) Ophthalmic- Mydriatic- Phenylephrine
Glaucoma- Apraclonidine/ Brimonidine
F) Uterine- Isoxsuprine, Ritodrine
Abortions – Threatened & Habitual
G) Endocrinal - Hot flushes in menopause,